One of the key issues in the biology of herpes simplex virus (HSV) concerns the biochemical mechanism which determines the lytic-latent life cycle of the virus. Following a primary infection, an individual harbors the viral genome in the neurons of the sensory (trigeminal/sacral) ganglia where it remains in a latent state until complex stimuli induce reactivation and viral replication. Although little is known about the factors involved in determining the latent-lytic states of the virus, the expression of the viral Immediate Early genes may represent an important regulatory point in this process. Specifically, the C1 factor, a cellular protein which controls the regulation of these genes, is likely to play a critical role in the determination of the latent-lytic viral cycle. As no tissue culture system faithfully represents a latent HSV infection, studies have focused upon the use of recombinant viruses and transgenes in the mouse model system. To develop a genetic system to analyze the role of the C1 factor in cellular processes and in the regulation of the latent-lytic cycle of HSV, the forms and function of the mouse C1 homologue have been characterized. cDNAs and genomic clones which encode this protein were isolated and demonstrate that the mouse homologue is nearly identical to the human factor. In contrast to the ubiquitous expression of the C1 factor in cultured cells, the protein is not expressed in all tissues, indicating that it may contribute to the tissue tropism of the virus.